The long-range goal of this proposal is to control tumor growth by inducing fine selective B-cell tolerance against soluble tumor associated antigen (TA) and, thus selectively suppressing the formation of those antibodies which protect the tumor from destruction by cytotoxic T lymphocytes without suppressing the formation of those antibodies which participate in a tumor rejection mechanism. The short-range goal of the proposal is to determine conditions for induction of selective B-cell tolerance against TA in vitro in cultures of mouse spleen cells as well as in vivo in mice, and to determine the role of the acompanying decrease in humoral antibodies (blocking, enhancing, cytotoxic and arming etc.) on the host's rejection of tumors. TA will be extracted from a high immunogenic drug-resistant subline of syngeneic L1210 lymphoma which has high density of TA. Solubilized TA will be used in various physical forms, or as antigen-antibody complex, or after chemical as well as biological modification to tolerize B-cells selectively. Quantitative assessment of B-cell response will be made by 1) plaque assay for antibody forming cells using the lymphoma cells as target, and 2) test of cytolysis of the lymphoma or radioimmunoassay using I125-labeled soluble TA for secreted antibodies. In parallel, T-cell mediated activities will be measured by testing various functional indicators of T-cells such as 1) tests for cell-mediated lysis with Cr51-release assay, 2) tests for lymphokine production such as migration inhibition factor.